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עמוד בית
Sat, 20.07.24

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May 2006
R. Rubinshtein, D.A. Halon, A. Kogan, R. Jaffe, B. Karkabi, T. Gaspar, M.Y. Flugelman, R. Shapira, A. Merdler and B.S. Lewis

Background: Emergency room triage of patients presenting with chest pain syndromes may be difficult. Under-diagnosis may be dangerous, while over0diagnosis may be costly.

Objectives: To report our initial experience with an emergency room cardiologist-based chest pain unit in Israel.

Methods: During a 5 week pilot study, we examined resource utilization and ER [1] diagnosis in 124 patients with chest pain of uncertain etiology or non-high risk acute coronary syndrome. First assessment was performed by the ER physicians and was followed by a second assessment by the CPU[2] team. Assessment was based on the following parameters: medical history and examination, serial electrocardiography, hematology, biochemistry and biomarkers for ACS[3], exercise stress testing and/or 64-slice multi-detector cardiac computed tomography angiography. Changes in decision between initial assessment and final CPU assessment with regard to hospitalization and utilization of resources were recorded.

Results: All patients had at least two cardiac troponin T measurements, 19 underwent EST[4], 9 echocardiography and 29 cardiac MDCT[5]. Fourteen patients were referred for early cardiac catheterization (same/next day). Specific working diagnosis was reached in 71/84 patients hospitalized, including unstable angina in 39 (31%) and non-ST elevation myocardial infarction in 12 (10%). Following CPU assessment, 40/124 patients (32%) were discharged, 49 (39%) were admitted to Internal Medicine and 35 (28%) to the Cardiology departments. CPU assessment and extended resources allowed discharge of 30/101 patients (30%) who were initially identified as candidates for hospitalization after ER assessment. Furthermore, 13/23 (56%) of patients who were candidates for discharge after initial ER assessment were eventually hospitalized. Use of non-invasive tests was significantly greater in patients discharged from the ER (85% vs. 38% patients hospitalized) (P < 0.0001). The mean ER stay tended to be longer (14.9 ± 8.6 hours vs. 12.9 ± 11, P = NS) for patients discharged. At 30 days follow-up, there were no adverse events (myocardial infarction or death) in any of the 40 patients discharged from the ER after CPU assessment. One patient returned to the ER because of chest pain and was discharged after re-assessment. 

Conclusions: Our initial experience showed that an ER cardiologist-based chest pain unit improved assessment of patients presenting to the ER with chest pain, and enhanced appropriate use of diagnostic tests prior to decision regarding admission/discharge from the ER.


 




[1] ER = emergency room

[2] CPU = chest pain unit

[3] ACS = acute coronary syndrome

[4] EST = exercise stress testing

[5] MDCT = multi-detector cardiac computed tomography angiography


R. Kannai and I.R. Chertok

The Ashkenazi-Jewish population is at increased risk for several recessively inherited disorders. While some of the disorders have severe or fatal symptom manifestations, others, such as non-neuronopathic Gaucher disease, do not usually pose a serious, life-threatening illness. Many healthcare centers in Israel offer prenatal panel screening. Controversy exists over the inclusion of Gaucher disease in the panel screening, especially since Gaucher disease screening lacks prognostic reliability. Most screening participants do not discriminate between the specific tests in the panel and are unable to discern between severe, life-threatening diseases and those that are less severe and even treatable. By including screening for Gaucher in the panel screening program, there is risk of a "panel effect," leading to termination of a pregnancy positive for Gaucher disease, without sufficient knowledge and understanding of the disease. Increasing medical and public awareness and knowledge of the disease, its prognosis and treatment options may reduce the rate of under-informed abortions associated with prenatal screening of Gaucher disease.

April 2006
G. Asher and Y. Shaul

Ubiquitin-proteasome degradation is a key cellular process involved in almost every aspect of cell life. According to the current concept, proteins are stable unless they are marked by poly-ubiquitination for degradation by the 26S proteasomes. A new twist in the concept became evident while studying the degradation of the tumor suppressor p53, a protein that appeared to satisfy this principle. We have discovered that native p53 is also prone to ubiquitin-independent 20S proteasomal degradation, suggesting that certain proteins are inherently unstable. We further found that this process of degradation is mediated by 20S proteasomes and inhibited by NADH quinone oxidoreductase 1. Our recent findings together with previous observations of ubiquitin-independent degradation suggest the existence of ubiquitin-independent mechanisms for proteasomal protein degradation in the cells.

 
 

Y. Mosesson and Y. Yarden

Polyubiquitylation of cellular proteins has long been recognized as a prelude to a degradative fate in proteasomes. In recent years, however, ubiquitin conjugation has emerged as a regulatory strategy of considerable versatility. Most notably, monoubiquitylation is attributed an intimate role in trafficking of membrane proteins between various cellular compartments. Diverse classes of transmembrane proteins from across the eukaryotic spectrum (e.g., epidermal growth factor-receptor and other receptor tyrosine kinases) become modified with monoubiquitin molecules. Monoubiquitylation of substrates, in turn, regulates both their endocytosis at the plasma membrane and sorting in endosomes for delivery to lysosomes or vacuoles. A mechanistic rationale lies in the identification of a growing list of ubiquitin-binding domains carried by a variety of endocytic adaptor proteins. Thus, ubiquitin-conjugated membrane proteins may form extensive contacts with the endocytic machinery. Further, ubiquitin-binding adaptors and other endocytic components are, likewise, often monoubiquitylated. In this case, ubiquitin conjugation may serve to enhance intermolecular avidity in cargo-bound endocytic complexes, or alternatively, to mediate timely inactivation of ubiquitin-binding adaptors. Interestingly, the ubiquitin/endocytosis interface is appropriated by pathogenic organisms, for instance, during budding of viruses from host-infected cells. Moreover, compromised ubiquitin-mediated transport of certain signaling receptors is associated with disease states, including oncogenic transformation.

 

 
 

E. Rabinovich, D. Bussi, I. Shapira, G. Alalouf, C. Lipson, Y. Elkabetz, M. Glickman, M. Bajorek and S. Bar-Nun
L. Kaplun, Y. Ivantsiv, A. Bakhrat, R. Tzirkin, K. Baranes, N. Shabek, and D. Raveh

We describe a unique E3, the F-box protein, Ufo1, of yeast. Ufo1 recruits the mating switch endonuclease, Ho, to the SCF complex for ubiquitylation. In addition to the F-box and WD40 protein-protein interaction domains found in all F-box proteins, Ufo1 has a unique domain comprising multiple copies of the ubiquitin-interacting motif. Ufo1 interacts with the UbL-UbA protein, Ddi1, via its UIMs[1], and this is required for turnover of SCF Ufo1 complexes. This is a novel function for an UbL-UbA protein. Deletion of the genomic UFO1 UIMs is lethal and our data indicate that Ufo1ΔUIM acts as a dominant negative leading to inhibition of the SCF pathway of substrate degradation and to cell cycle arrest. Furthermore, we found that Ddi1 is required for the final stages of degradation of Ho endonuclease. In the absence of Ddi1, Ho does not form a complex with the 19S RP and is stabilized. Stabilization of Ho leads to perturbation of the cell cycle and to the formation of multi-budded cells. Our experiments uncover a novel role for the ubiquitin-proteasome system in maintenance of genome stability.






[1] UIM = ubiquitin-interacting motif


C. Weissman, L.A. Eidelman, R. Pizov, I. Matot, N. Klein and R. Cohn

Background: Anesthesiology is a vital specialty that permits the safe and humane performance of painful procedures. Most Israeli anesthesiologist are immigrants, while only a minimal number of Israeli medical school graduates enter the specialty. Unfortunately, the supply of immigrant physicians is declining due to falling immigration rates.

Objectives: To examine the current Israeli anesthesiology workforce and project future needs.

Methods: Demographic and professional information about Israeli hospital anesthesiologists was solicited from anesthesiology department heads. Data were also gathered about the past, present and projected future growth, age distribution and birth rate of the Israeli population. Needs and demand-based analyses were used to project future anesthesiology workforce requirements.

Results: Data about 711 anesthesiologists were obtained from 30 hospital anesthesiology department heads. Eighty-seven anesthesiologists (12.2%) graduated from Israeli medical schools and 459 (64.6%) graduated from medical schools in the former Soviet Union. Among the 154 anesthesiology residents were ≤ 40 years old, and only 13 (8.4%) graduated from Israeli medical schools There are approximately 10.8 anesthesiologists per 100,000 population. Projections for 2005–2015 revealed a need for 250–300 new anesthesiologists.
Conclusions: The anesthesiology workforce is predominantly composed of immigrants. This has vast implications for the future viability of the specialty because of the continuing reduction in immigration, the lack of interest in the specialty by Israeli medical school graduates, and the projected need for many new anesthesiologists to replace retirees and to provide care to a growing and aging population

F. Magora, S. Cohen, M. Shochina and E. Dayan

Background: Virtual reality immersion has been advocated as a new effective adjunct to drugs for pain control. The attenuation of pain perception and unpleasantness has been attributed to the patient's attention being diverted from the real, external environment through immersion in a virtual environment transmitted by an interactive 3-D software computer program via a VR[1] helmet.


Objectives: To investigate whether VR immersion can extend the amount of time subjects can tolerate ischemic tourniquet pain.


Methods: The study group comprised 20 healthy adult volunteers. The pain was induced by an inflated blood pressure cuff during two separate, counterbalanced, randomized experimental conditions for each subject: one with VR and the control without VR exposure. The VR equipment consisted of a standard computer, a lightweight helmet and an interactive software game.


Results: Tolerance time to ischemia was significantly longer for VR conditions than for those without (P < 0.001). Visual Analogue Scale (0–10) ratings were recorded for pain intensity, pain unpleasantness, and the time thought about pain. Affective distress ratings of unpleasantness and of time thought about pain were significantly lower during VR as compared with the control condition (P < 0.003 and 0.001 respectively).

Conclusions: The VR method in pain control was shown to be beneficial. The relatively inexpensive equipment will facilitate the use of VR immersion in clinical situations. Future research is necessary to establish the optimal selection of clinical patients appropriate for VR pain therapy and the type of software required according to age, gender, personality, and cultural factors.






[1] VR = virtual reality


O. Bronshtein, V. Katz, T. Freud and R. Peleg

Background: Physicians in the community work on a tight and often pressured schedule; verbal and non-verbal techniques to terminate the patient-physician encounter are therefore necessary.

Objectives: To characterize ways of terminating the encounter.

Methods: Using a structured questionnaire we observed seven family physicians and nine consultants and recorded patient-physician encounters to assess techniques for terminating the encounter.

Results: In all, 320 encounters were recorded, 179 (55.9%) by consultants and 141 (44.1%) by family physicians. The mean duration of the encounters was 9.02 ± 5.34 minutes. The mean duration of encounters with family physicians was longer than consultants (10.39 vs. 7.93 minutes, P < 0.001). In most cases the encounter ended with the patient receiving printed documentation from the physician (no difference between family physicians and consultants). Consultants were more likely to end the encounter with a positive concluding remark such as “feel good” or “be well” (P < 0.01). There was no single occasion where termination of the encounter was initiated by the patient.

Conclusions: Giving a printed document to the patient appears to be perceived by both patients and physicians as an accepted way to end an encounter. Another good way to end the encounter is a positive greeting such as “feel good” or “be well.”
 

G. Ofer, B. Rosen, M. Greenstein, J. Benbassat, J. Halevy and S. Shapira

Background: Debate continues in Israel as to whether to allow patients in public hospitals to choose their physician in return for an additional, out-of-pocket payment. One argument against this arrangement is that the most senior physicians will devote most of their time to private patients and not be sufficiently available to public patients with complex cases.

Objectives: To analyze the patterns of surgical seniority in Jerusalem hospitals from a number of perspectives, including the extent to which: a) opting for private care increases the likelihood of being treated by a very senior surgeon; b) public patients undergoing complex operations are being treated by very senior surgeons, c) the most senior surgeons allocate a significant portion of their time to private patients.

Methods: Demographic and clinical data were retrieved from the operating room records of three of the public hospitals in Jerusalem for all 38,840 operations performed in 2001. Of them, roughly 6000 operations (16%) were performed privately. Operations were classified as "most complex," "moderately complex" and "least complex" by averaging the independent ratings of eight medical and surgical experts. The surgeon's seniority was graded as "tenured" (tenured board-certified specialists, including department heads), "senior" (non-tenured board-certified specialists), and "residents." For each operation, we considered the seniority of the lead surgeon and of the most senior surgeon on the surgical team.

Results: The lead surgeon was of tenured rank in 99% of the most complex private cases and 74% of the most complex public cases, in 93% of the moderately complex private and 35% of the moderately complex public cases, and in 92% of the least complex private and 32% of the least complex public cases. The surgical team included a tenured physician in 97%, 66%, and 53% of the most complex, moderately complex, and least complex public operations, respectively. In both private and public cases, a board-certified (tenured or senior) specialist was a member of the surgical team for almost all of the most complex and moderately complex operations. On average, over half of the operations in which the lead surgeon was a department head were performed on public patients. Among tenured surgeons, those who spent more hours than their colleagues leading private operations also tended, on average, to spend more hours leading public operations.

Conclusions: Private patients have an advantage over public patients in terms of the seniority of the lead surgeon. However, there is also substantial involvement of very senior surgeons in the treatment of public patients, particularly in those cases that are most complex. 

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